The present invention relates to intracorporeal gas exchange devices, systems and methods and, particularly, to devices, systems and method to effect gas exchange within a patient's vascular structure.
The following information is provided to assist the reader to understand the invention disclosed below and the environment in which it will typically be used. The terms used herein are not intended to be limited to any particular narrow interpretation unless clearly stated otherwise in this document. References set forth herein may facilitate understanding of the present invention or the background of the present invention. The disclosure of all references cited herein are incorporated by reference.
Lung disease remains one of the major healthcare problems present in the United States today. Two significant contributors to lung disease are acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD).
Acute respiratory distress syndrome is defined as a severe syndrome of inflammation and increased vascular permeability that is associated with a constellation of clinical, radiologic, and physiologic abnormalities. It is a non-cardiogenic, acute respiratory complication characterized by a profound reduction in systemic oxygenation or ventilation, with an in-hospital mortality rate of 38.5%. ARDS develops as a result of injury to the endothelium and epithelial layers of the alveolar membrane from stimuli such as sepsis, infection or trauma. The breakdown of the capillary-alveolar barrier leads to alveolar flooding and an eventual deterioration of gas exchange capability.
In contrast to ARDS, chronic obstructive pulmonary disease is a persistent, irreversible condition that slowly progresses over time. COPD refers to the existence or co-existence of chronic bronchitis and emphysema and is characterized by obstructed airways, enlarged air spaces and destruction of lung parenchyma, occlusion of small airways, and reduced lung elasticity. When compared to normal, healthy lung function, patients with advanced stages of COPD can experience 10 to 20 times the work necessary to facilitate breathing.
Hospital treatment for ARDS, acute exacerbations of COPD, and advanced COPD exist in three broad generalizations: pharmacological, mechanical ventilation and application of an extracorporeal membrane device (artificial lung). The treatment modalities depend on the severity of the disease as well as patient response to prior therapies. As indicated by the high mortality rates for the lung conditions, however, each therapy has associated limitations which can interrupt patient discharge from the hospital and/or recovery.
The least invasive and first line of defense in treating lung failure is to administer drugs that may improve the ailing condition. Multiple pharmacologic strategies have been investigated since the 1960's, but despite therapeutic benefits, none of the investigated treatments have demonstrated an ability to improve patient survival.
Mechanical ventilation is the most common therapy and serves to maintain respiratory function by rhythmically inducing a controlled flow of air into the lungs. In healthy persons, normal breathing consists of contracting the diaphragm to distend the lungs and create a negative pressure from atmosphere to lungs forcing fresh air in. Following oxygen and carbon dioxide gas exchange, the diaphragm relaxes compressing the lungs and forcing expiratory air to the external environment. Mechanical ventilation creates this effect but in an opposing manner; fresh air is driven into the lungs by positive pressure and expiratory air is pumped out of the lungs by a negative pressure.
Mechanical ventilation treatment is associated with multiple shortcomings termed ventilator-induced lung injury, or VILI. VILI covers a range of detrimental insults to the lung that can postpone recovery, cause unfavorable outcomes, or even intensify preexisting injury.
The third clinical therapy being administered utilizes a membrane oxygenator and accompanying flow circuit. The treatment is denoted as extracorporeal membrane life support (ECLS), often times referred to as extracorporeal membrane oxygenation (ECMO). An ECLS device processes patient blood by adding oxygen and removing carbon dioxide through fiber membrane technology, replicating the natural gas exchange function of the lungs.
ECLS is employed under circumstances of severe, reversible respiratory failure or to patients responding adversely to all advanced modes of mechanical ventilation. Operation of the circuit relies on a pump to draw blood from the vena cava, transport it through the membrane oxygenator, and return the blood either to the right atrium (venovenous bypass) or aorta (venoarterial bypass). Patients still receive mechanical ventilation while on ECLS, however settings are reduced to minimize VILI as a result of the ability of the oxygenator to exchange blood gases. With less required work from the lungs, ECLS permits physiological complications to abate and the therapy can be applied for weeks barring complications.
Limitations of ECLS primarily arise from external circuitry and artificial blood contacting surfaces. To avert thrombosis within the circuit, patient blood is continuously anticoagulated and bleeding is a major risk whether internal (intercranial) or from cannula dislodgement. Patients are paralyzed and/or heavily sedated to minimize movement causing dislodgement, which creates a high risk scenario for decubitis ulcers. Also, the continuous exposure of the blood to artificial surfaces causes platelets to adhere and/or alter function (thrombocytopenia) requiring the patient to receive multiple platelet transfusions. In addition, the ECLS circuit must be constantly monitored for mechanical failures such as tubing degradation, oxygenator or pump failure, and presence of gaseous emboli or clot formation. Other noted complications include sepsis and renal failure. Finally, ECLS requires a multidisciplinary team to provide care. Staffing and overall cost of the procedure, as well as restriction to major medical centers are further limitations to providing this therapy.
Recently, there have been attempts to develop intracorporeal artificial lung devices. Percutaneous, intravascular respiratory support therapy, which refers to treatments employing a gas exchange device or an artificial lung device within the vasculature of a patient to supplement lung function, can be used as an additional and/or alternative approach to treating ARDS and acute exacerbations of COPD. Such devices typically use hollow fiber membrane or HFM technology to achieve gas exchange, oxygenating blood and removing carbon dioxide. In most situations, carbon dioxide removal is a primary goal of intravascular devices since sufficient oxygenation levels can be attained in the clinical setting through nasal oxygen or specific ventilation modes.
The ability of intravascular respiratory support devices to facilitate carbon dioxide removal from the circulation provides an advantage over sole mechanical ventilation strategies. By regulating hypercapnia (or elevated carbon dioxide levels in the blood), intravascular respiratory therapy can allow ventilation at lower tidal volumes and pressures and thereby eliminate the deleterious effects that often develop with mechanical ventilation. Decrease in mechanical ventilation intensity to support patients has been demonstrated to improve mortality rates. In addition, the diseased lung tissue experiences a lower workload since the device itself is performing partial respiratory function. The reduced workload allows the injured tissue to rest and may improve tissue recovery.
ECLS is able to regulate hypercapnia but is associated with a number of complications resulting from blood circulating outside the body. Utilizing an intracorporeal/intravascular device eliminates external circuitry, thereby lessening the risks of thrombocytopenia and activation of complement resulting from artificial surfaces. Less artificial surface can also result in lower anticoagulation levels thereby decreasing bleeding risks. Overall implementation of the intravascular respiratory therapy is easier than ECLS making it less demanding on hospital resources, less expensive, and potentially available in more hospitals.
Factors regulating gas exchange in the intravascular devices include gas partial pressures in both blood and fiber lumens, total HFM surface area, fiber bundle geometry and relative velocity at which the blood passes by the fiber surfaces. A concentration boundary layer that forms near the external walls of the individual fibers can result in significant resistance to diffusion that limits gas exchange. The boundary layer forms as a result of blood flow patterns around the fiber walls.
Existing intravascular devices can be categorized as either passive or active by the means in which boundary layer reduction is approached. Passive devices rely on blood flowrates and fiber bundle geometry to mix flow patterns and disrupt layer formation near stationary fibers. Active devices implement motion to the fiber membranes and or to the blood subjacent to the fiber membranes to disrupt boundary layer formation. In general, to increase gas exchange, additional surface area can be provided to boost overall diffusion and/or boundary layers can be reduced to decrease mass transfer resistance. High relative blood velocity to fibers facilitates boundary layer reduction.
As clear to those skilled in the art, a relatively small size is beneficial for intracorporeal/intravascular respiratory assist devices. Such devices can, for example, be inserted into a patient's vascular structure in the manner of a catheter. Reducing insertion size of the device is desirable to prevent tissue damage and facilitate placement. However, limiting the size of the intravascular device also results in limitations upon surface area of the gas exchange membrane system, thereby limiting gas exchange. Further, the amount of motion that can be imparted to blood and/or fibers to increase gas exchange efficiency is limited by potential damage to surrounding tissue and to the blood. Previously studied intracorporeal/intravascular devices have met with only limited success as a result of these limitations.
It thus remains desirable to develop improved intracorporeal gas exchange devices, systems and methods that are safe, effective, and/or amenable to easy insertion.